This project is concerned with studies on the mechanism of activation of human plasminogen by streptokinase and reasons for the insensitivity of other species of plasminogen by this bacterial protein. These studies are significant in the attempt to manipulate the fibrinolytic system for the benefit of man. Since this can be done only with knowledge of the mechanism of activation of plasminogen. For these same reasons we will attempt to understand the metabolism of plasminogen and its isozymes in animals. Factors that can increase or decrease the levels of selected plasminogen isozymes may also be beneficial in controlling selective plasminogen properties, depending on the role of the isozymes effected.